text: Mycophenolic acid is a Penicillium metabolite that was originally prepared via a key benzannulation step.  An alkyne and a cyclobutenone were reacted to form a substituted phenol in a single step in a 73% yield (Scheme 14). Mycophenolic acid was prepared in nine steps in an overall yield of 17-19%.
  In the synthesis of highly substituted indoles performed by Danheiser, the key step was a benzannulation reaction using cyclobutenone and ynamides to produce highly substituted aniline derivatives. In this case, the ortho position can be functionalized with various substituents. Following the benzannulation reaction with various heterocyclization reactions can provide access to substituted indoles (Scheme 15).
  Danheiser also used the benzannulation with ynamides for the synthesis of polycyclic benzofused nitrogen heterocycles followed by ring-closing metathesis (Scheme 16) for the total synthesis of (+)-FR900482, an anticancer agent.
  Kowalski used the benzannulation reaction with siloxyacetylenes for the first time, reacting them with cyclobutenones to synthesize a substituted phenol for the total synthesis of Δ-6-tetrahydrocannabinol (Scheme 17).
  The benzannulation reaction was used by Smith in the total synthesis of cylindrocyclophanes specifically (−)-Cylindrocyclophane F. He utilized the reaction of a siloxyalkyne and a cyclobutenone to construct the dihydroxyl aromatic intermediate for an olefin metathesis reaction to access the target (Scheme 18).
  An outstanding application of Danheiser benzannulation in 6-step synthesis of dictyodendrins was demonstrated by Zhang and Ready. They obtained the cyclobutenone substrate using a hetero-[2+2] cycloaddition between aryl ynol ethers (aryl ketene precursors), and the following benzannulation enabled the rapid construction of the carbazole cole of dictyodendrins F, H and I.  The successful usage of Danheiser benzannulation allows Zhang and Ready to achieve the so-far shortest synthesis of dictyodendrin natural products.